title: Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non-small cell lung cancer.
abstract: The identification of chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues and the demonstration that the first-in-class ALK tyrosine kinase inhibitor, crizotinib, can effectively target these tumors represent a significant advance in the evolution of personalized medicine for NSCLC. Single-arm studies demonstrating rapid and durable responses in the majority of ALK-positive NSCLC patients treated with crizotinib have been followed by a randomized phase III clinical trial in which superiority of crizotinib over chemotherapy was seen in previously treated ALK-positive NSCLC patients. However, despite the initial responses, most patients develop acquired resistance to crizotinib. Several novel therapeutic approaches targeting ALK-positive NSCLC are currently under evaluation in clinical trials, including second-generation ALK inhibitors, such as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90 inhibitors.
authors.affiliation: 1] Department of Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia [2] Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Solomon
authors.affiliation: Pfizer, La Jolla, California, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Wilner
authors.affiliation: Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Shaw
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D002986:Clinical Trials as Topic; D000077547:Crizotinib; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases